In utero exposure to environmental chemicals, such as synthetic
phenols, may alter DNA methylation in different tissues, including placenta - a critical organ for fetal development. We studied associations between prenatal urinary
biomarker concentrations of synthetic
phenols and placental DNA methylation. Our study involved 202 mother-son pairs from the French EDEN cohort. Nine
phenols were measured in spot urine samples collected between 22 and 29 gestational weeks. We performed DNA methylation analysis of the fetal side of placental tissues using the IlluminaHM450 BeadChips. We evaluated methylation changes of individual CpGs in an adjusted epigenome-wide association study (EWAS) and identified differentially methylated regions (DMRs). We performed mediation analysis to test whether placental tissue heterogeneity mediated the association between urinary
phenol concentrations and DNA methylation. We identified 46 significant DMRs (≥5 CpGs) associated with
triclosan (37 DMRs),
2,4-dichlorophenol (3),
benzophenone-3 (3), methyl- (2) and
propylparaben (1). All but 2 DMRs were positively associated with
phenol concentrations. Out of the 46 identified DMRs, 7 (6 for
triclosan) encompassed imprinted genes (APC, FOXG1, GNAS, GNASAS, MIR886, PEG10, SGCE), which represented a significant enrichment. Other identified DMRs encompassed genes encoding
proteins responsible for cell signaling, transmembrane transport, cell adhesion, inflammatory, apoptotic and immunological response, genes encoding
transcription factors,
histones,
tumor suppressors, genes involved in
tumorigenesis and several
cancer risk
biomarkers. Mediation analysis suggested that placental cell heterogeneity may partly explain these associations. This is the first study describing the genome-wide modifications of placental DNA methylation associated with pregnancy exposure to synthetic
phenols or their precursors. Our results suggest that cell heterogeneity might mediate the effects of
triclosan exposure on placental DNA methylation. Additionally, the enrichment of imprinted genes within the DMRs suggests mechanisms by which certain exposures, mainly to
triclosan, could affect fetal development.